Inclusion of Methoxybutropate in β-and Hydroxypropyl β-Cyclodextrins: Comparison of Preparation Methods

Interactions between methoxybutropate and β-cyclodextrin or hydroxypropyl β-cyclodextrin and the possibility of obtaining inclusion complexes have been evaluated by phase solubility diagram, HPLC, DSC, and x-ray diffractometry. Solid inclusion complexes were prepared by spray drying, kneading, and solid dispersion. The dissolution profiles of the obtained powders were studied in order to define the most appropriate cyclodextrin preparation method and molar ratio to use in the production of methoxybutropate inclusion complexes     

The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain

In the present study, the effects of benzodiazepines (diazepam) were evaluated in terms of cortical excitability changes, as tested with transcranial magnetic simulation (TMS). In particular, analyzed were drug-induced changes regarding two selected parameters of TMS: (1) the cortical excitability threshold and (2) the silent period duration (SP). For this purpose, we evaluated the effects of long-term therapy with diazepam in the patients affected by anxiety disorders and the changes induced by single oral doses of diazepam in both healthy controls and patients. In addition, we tested cortical excitability changes in two 'extreme conditions' where a considerable concentration of serum benzodiazepine-like activity was reached, as represented by diazepam overdose and idiopathic recurrent stupor (IRS). In both groups of patients, a significant increment of motor threshold was found, while in the overdose patients, the SP was also increased. The administration of flumazenil in these two conditions was followed by a prompt reversal effect, consisting of a return to normal cortical excitability parameters. The long-term usage of diazepam in patients with anxiety disorders is associated with significantly increased threshold; the increased value of these parameters was temporarily further enhanced by the administration of a single oral dose of diazepam, which, in normal control subjects, is not associated with changes of cortical excitability. The results of this study reveal that different physio-pathological conditions induced by the influence of benzodiazepine and its antagonist are reflected in excitability changes which attest to the involvement and modification of cortical GABAergic activity.     

Dissolution of Suppositories V: Influence of Aging on Aspirin Release from Polyethyleneglycol Suppositories with and Without Crospovidone

This report details the effect of aging on release of aspirin from four PEG blends containing crospovidone as a disintegrant in concentrations of 0, 0.5, 1 and 5%. It has been reported in the literature that release from suppository formulations is often altered upon aging. In this experiment, suppositories containing 350 mg aspirin were dissolved in 1,000 mls of pH 8.0 dissolution fluid, at 37.5° with an agitation rate of 50 rpm. Suppositories were designated as fresh (less than 10 days old), 4 months old and 6 months old. Aspirin was assayed at 265 nm. Dissolution profiles as well as dissolution half-times were reported. Aging had little effect on Base A and Base B. However, Ease C exhibited an ambiguous effect in that the dissolution half-times were inconsistent. Base D exhibited a dramatic change in release upon aging in that the dissolution half-times increased from 23 minutes to 55 minutes with 1/22 crospovidone. It is hypothesized that Base D stabilized when larger amounts of crospovidone are used although the exact mechanism of this stabilization is unknown     

Interactions between lonidamine and beta- or hydroxypropyl-beta-cyclodextrin

Equilibrium dialysis and Scatchard plots were used to establish that human and rabbit paraoxonases both have two calcium binding sites. Independent-site and stepwise constant analyses were used to calculate a higher affinity site (Kd1) of 3.6 +/- 0.9 x 10(-7) M for human A paraoxonase, and 1.4 +/- 0.5 x 10(-8) M for rabbit paraoxonase, and a lower affinity site (Kd2) of 6.6 +/- 1.2 x 10(-6) M for human A paraoxonase, and 5.3 +/- 0.94 x 10(-6) M for rabbit paraoxonase. In both species, the higher affinity sites were found to be essential to maintain hydrolytic activity; complete removal of calcium led to irreversible inactivation. The lower affinity sites were required for catalytic activity, and their binding of calcium was reversible. Experimentally estimated values of Kd2 based on the concentration of calcium required to obtain half the maximum enzymatic activity were 3 microM for human A and B paraoxonases, and also in the order of 3 microM for rabbit paraoxonase, using three different substrates. Calcium was the only metal found that protects against denaturation and also confers hydrolytic activity with these two mammalian paraoxonases.     

Laparoscopic surgery in varicocele: description of the technique and preliminary data

Gas chromatography/mass spectrometry with selected-ion monitoring (GC/MS-SIM) method were used to analyze 23 selected phenols in natural and drinking waters by an in situ acetylation technique. This method was suitable for determining phenol concentrations at the ng/L level because of less background interference and better recoveries. The application range for all these phenols was from 0.01 or 0.04 to 10 micrograms/L, using a 800 ml water sample. The levels of trace phenols in four Taiwan water treatment plants were in the range of 12-312 ng/L. The polychlorinated phenols, namely 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol, and pentachlorophenol, were evaluated for their ability to induce deoxyribonucleic acid (DNA) damage using a DNA precipitation assay employing mouse embryonic fibroblast cells (C3H10T1/2) with or without a liver microsomal activation system. These agents exhibited a weak positive response when microsomal activation enzymes were present in this assay. When the tetrachlorohydroquinone, a toxic metabolite of pentachlorophenol, was measured by the same method without the activation system, a significant and dose-dependent DNA damage was found. This result indicates that in the evaluation of the carcinogenic potential of these agents, their corresponding metabolites should be taken into consideration. DNA strand breakage caused by these active metabolites may play an important role in the tumorigenetic process of polychlorinated phenols.     

Comparison of erythrocyte uridine sugar nucleotide levels in normals, classic galactosemics, and patients with other metabolic disorders

By limiting galactosylation mechanisms, a cellular deficiency of the uridine sugar nucleotide, UDPgalactose, has been implicated as a cause of the long-term complications seen in patients with classic galactosemia despite dietary treatment. As a result, great interest has been generated in the accurate assessment of UDPgalactose, as well as UDPglucose, from which UDPgalactose may be derived by the function of a ubiquitous, active UDPgalactose-4-epimerase. Since several series of values for the concentration of these compounds in red blood cells (RBCs) of galactosemics have been flawed by the use of methods subsequently shown to be unsuitable, we have quantified erythrocyte UDPgalactose and UDPglucose levels by an accurate high-performance liquid chromatography (HPLC) assay in 116 normals, 76 galactosemics, and 39 patients with other metabolic disorders. These large groups have permitted the evaluation of age, diet, and genotype as influential factors in the steady-state RBC levels of the sugar nucleotides. The data show that age is an important determinant of RBC levels, with children younger than 10 years having higher values than individuals older than 10 years. Mean UDPgalactose levels in galactosemic children younger than 10 years and those older than 10 years were 30% and 18% lower, respectively, than levels in comparable normals. Although the mean differences were highly significant, there was considerable overlap of individual values. There was no difference in UDPglucose levels between galactosemics and normals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of spin inaccuracy on PMD reduction in spun fibers

Spinning a fiber is the most viable and used technique to reduce polarization mode dispersion (PMD). Many papers have shown that by properly tuning the spin parameters, the differential group delay (DGD) of spun fibers can be greatly reduced. However, the precision with which these optimal profiles are practically implemented may be a problem. In this paper, we perform a statistical analysis of the effects that spin inaccuracy may have on fiber PMD, quantifying how the random uncertainty on spin parameters impairs the DGD. Some preliminary experimental results about spin-induced PMD reduction are also reported.